Specificity of antibody responses affected by extracorporeal immunoadsorption of plasma over columns of protein A silica

Abstract

A relationship is described between the interaction of circulating immune complexes (CIC) from plasma with staphylococcal protein A immunoadsorption treatment columns and modulation of antibody responses related to the specific CIC. Eluates from the initial immunoadsorption columns used to treat a series of patients with breast adenocarcinoma, cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (C-TTP/HUS), or immune thrombocytopenic purpura (ITP) were evaluated for disease-specific CIC containing Lex glycosphingolipid (Lex gl) adenocarcinoma-associated antigens or platelet autoantibody (anti-GPIIb/IIIa), together with the corresponding neutralizing antibody [anti-F(ab')2], and for nonspecific CIC containing cytomegalovirus (CMV) or herpes simplex virus type 1 (HSV-1) antigens. In addition, the levels of antibodies directed against CMV, HSV-1, Lex gl, and GPIIb/IIIa antigens, as well as anti-F(ab')2 antibodies, were compared in pretreatment and posttreatment serum samples. Columns used to treat breast adenocarcinoma patients contained only Lex gl CIC, and the only immunologic change observed after treatment was significant increases in anti-Lex gl antibodies in some patients. Columns used to treat C-TTP/HUS patients contained anti-GPIIb/IIIa-anti-F(ab')2 CIC, in addition to Lex gl CIC. After treatment, significant increases in anti-Lex gl and anti-F(ab')2 antibodies and significant decreases in anti-GPIIb/IIIa antibodies were observed in some patients. Columns used to treat ITP patients only exhibited anti-GPIIb/IIIa-anti-F(ab')2 CIC, and after treatment only decreases in anti-GPIIb/IIIa and increases in anti-F(ab')2 antibodies were observed in some patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Immune Modulation Associated with Extracorporeal Immunoadsorption Treatments Utilizing Protein A/Silica Columns

“…In association with immunoadsorption treatments, there was a concomitant decrease in the levels of IgG idiotype (IgG autoantibody or IgG alloantibody) and corresponding IgG antiidiotype. These results may also explain data reported in a previous study in which decreased levels of anti-F(ab')2 activity appeared to return to normal levels as a consequence of immunoadsorption therapy (19). Because pretreatment samples contain elevated levels of IgG idiotype and corresponding antiidiotype, they may block anti-F(ab'), activity resulting in what appears to be depressed anti-F(ab')2 activity.…”

Successful Treatment by Radiation and Hormone Therapy of Isolated Local Recurrence of Breast Cancer 24 Years After Mastectomy Accompanied by Immune Thrombocytopenia: a Case Report

“…ITP or autoimmune hemolytic anemia has been reported in association with lymphoid malignancies or solid tumors (Table 1). Immune thrombocytopenia with platelet destruction is strongly suggested by the combination of elevated PA-IgG or -lgM or antibodies against platelet glycoprotein Ib or llb/Illa (6)(7)(8)10,20). The levels ofPA-lgG or -lgM may correlate with tumor mass or with progressive disease (3,7), although our patient did not show such a clear correlation.…”

Removal of Pathogenic Autoantibodies by Immunoadsorption

“…Despite the limited volume of processed plasma, which does not allow significant removal of immunoglobulins or circulating immune complexes, this device has been shown to exert immune modulating effects. Its mode of action remains, however, somewhat obscure 15‐17. The Prosorba system is approved by the FDA for treatment of rheumatoid arthritis refractory to therapy with conventional drug regimens.…”

“…Its mode of action remains, however, somewhat obscure. [15][16][17] The Prosorba system is approved by the FDA for treatment of rheumatoid arthritis refractory to therapy with conventional drug regimens. This decision was largely based on the results of a prospective, controlled, randomized, and double-blinded study on 99 patients.…”